International Journal of

Environmental Research
and Public Health

Review
Gestational Diabetes: Overview with Emphasis
on Medical Management
Michelle Lende and Asha Rijhsinghani *
Division of Maternal and Fetal Medicine, Department of Obstetrics and Gynecology, Albany Medical Center,
Albany Medical College, Albany, NY 12208, USA; lendem@amc.edu
* Correspondence: rijhsia@amc.edu




Received: 27 October 2020; Accepted: 14 December 2020; Published: 21 December 2020


Abstract: With the rising trend in obesity, the incidence of gestational diabetes mellitus (GDM) and
perinatal complications associated with the condition are also on the rise. Since the early 1900s,
much knowledge has been gained about the diagnosis, implications, and management of gestational
diabetes with improved outcomes for the mother and fetus. Worldwide, there is variation in the
definition of GDM, methods to screen for the condition, and management options. The International
Association of Diabetes in Pregnancy Study Groups has published recommendations for a one-step
approach to screen pregnant women for GDM, in order to develop outcome-based criteria that can be
used internationally. However, management of GDM continues to be varied, and currently several
options are available for treatment of hyperglycemia during pregnancy. A review of various aspects
of GDM is discussed with a focus on the medical management during pregnancy, as practiced in
the United States.

Keywords: gestational diabetes

1. Introduction
A worldwide rising trend in obesity has been reported from 1975 to 2016, affecting females and
males alike [1]. In women, the rising obesity has led to an increase in the incidence of gestational diabetes
mellitus (GDM) as well as associated pregnancy and perinatal complications. Known non-modifiable
risk factors for predisposition to GDM include advanced maternal age, ethnicity, and family history of
type 2 diabetes mellitus [2]. Maternal obesity independently contributes to the development of GDM [3].
The Center of Disease Control (CDC) estimates that the incidence of GDM in the United States (US) is
about 10%. It is reported to be higher in some countries with rates as high as 17.8–41.9% when using
the International Association of Diabetes in Pregnancy Study Groups (IADPSG) GDM criteria [4,5].
In Western countries, a body mass index (BMI) of <25 Kg/m2 is considered normal.
The recommendations for pharmacotherapy in patients with GDM have evolved over the past
two decades. In this review, we provide an overview of the condition, with emphasis on the evolution
of medical management over the past century. We have included the recent data on the options for
medical management, as well as data on the current recommendations based on safety data of these
pharmacotherapeutic options during pregnancy.

2. Methods
This review was performed by including studies published in PubMed, Cochrane Library,
the national guidelines, and WHO-based guidelines. The search was performed using key words
that included “gestational diabetes”, “diabetes management”, and “pregnancy”. Recent publications,
randomized control trials, observational studies, review articles, meta-analyses, Cochrane reviews,
and current practice guidelines from national organizations were selected. Year of publication was not

Int. J. Environ. Res. Public Health 2020, 17, 9573; doi:10.3390/ijerph17249573 www.mdpi.com/journal/ijerph
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a limiting factor in this literature search. The publications included in this review were restricted to
English language. The diagnosis of GDM in this review is based on the definition recommended by
the American College of Obstetrics and Gynecology (ACOG). Articles on pharmacotherapy within
the last two decades for treatment of hyperglycemia in GDM are reviewed with emphasis on the recent
publications and recommendations.

3. Historical Aspects of Gestational Diabetes

Recognition of diabetes complicating pregnancy dates back to 1873 [6]. In 1910, it was proposed
that patients with gestational glycosuria be grouped into two categories, namely, pregnant women
suffering from true and persistent glycosuria and pregnant women who pass sugar in their urine
only when their diet contains a large amount of sugar or starch [7]. Subsequently, in a series of
468 pregnant women, 5 were documented with glycosuria with only one who was known to have
pre-pregnancy diabetes [8]. The author suggested that in cases where glycosuria occurred during
pregnancy, true diabetes might be “about to manifest itself”. From these early cases, it was recognized
that there is a difference between diabetes diagnosed prior to pregnancy and diabetes diagnosed
during pregnancy.
Due to recognition of the possibility of diabetes affecting a pregnancy, studies were conducted to
understand the effect of pregnancy on carbohydrate metabolism. The adverse effect of pregnancy on
carbohydrate metabolism was first documented in 1946 [9]. Hoet from Belgium performed animal
experiments to study carbohydrate metabolism during pregnancy [10]. The harmful effects of GDM
on pregnancy outcomes were subsequently reported. In 1946, while reporting on the effects of
hyperglycemia during pregnancy, the author documented the finding that fetal death can occur even
before the woman has symptoms of diabetes [11]. Subsequently, in 1959, the association of maternal
pre-diabetes with fetal macrosomia was published in Italy [12]. Two years later, O’Sullivan described
GDM as “unsuspected and asymptomatic” diabetes, which is elicited in response to a glucose tolerance
test during pregnancy [13]. At that time, the incidence of GDM was reported to be 1 in 116 [13].
Due to the recognition of the complications associated with GDM, a need for accurate and timely
diagnosis was realized [14,15]. In 1924, a 50-g glucose load was administered to a pregnant patient with
history of glycosuria, to determine if she had glucose intolerance [16]. The oral glucose tolerance test
(GTT) was described in 1932. In search of an ideal glucose screen, an intravenous glucose tolerance test
and a prednisone-glucose tolerance test were studied [17,18]. In 1961, O’Sullivan screened all pregnant
patients with a 50-g oral glucose load and when the one-hour venous blood sugar was ≥130 mg/dL,
the patient was considered screen-positive. At that time, patients were also classified as screen-positive
if the patient had a family history of diabetes, a prior fetal or neonatal death, congenital fetal anomaly,
prematurity, toxemia in two or more pregnancies, or a history of a prior baby that weighed 9 pounds
or greater. Patients screened as positive were administered a three-hour GTT [13].
By 1985, glucose screening was routinely being used in patients considered to be at “high risk” for
GDM [19]. Due to the varying definitions, the reported incidence of GDM ranged from 0.31% to 18%.
This led to the suggestion of using similar screening criteria by all centers, to help better understand
the condition and its impact on pregnancy.

4. Antenatal Glucose Screening

Various organizations attempted to establish population-based protocols to diagnose GDM [20].
In 1999, the WHO recommended a screening test of a 75-g anhydrous glucose load, following an
overnight fasting for 8–14 h, between 24 and 28 weeks’ gestation. The protocols suggested by
national and international organizations such as the IADPSG, American Diabetes Association (ADA),
and United Kingdom-based National Institute for Health and Care Excellence (NICE) and Canada
were recently reviewed [21]. Both a single-step and a two-step screening process during pregnancy
have been described. Based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study,
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the IADPSG recommended a single-step 2-h glucose tolerance test. After an overnight fast, a 75-g
glucose load is administered. The fasting 1-h and 2-h plasma glucose levels are checked.
Despite the ADA endorsing the one-step 75-g glucose load GTT in 2011 based on the IADPSG
criteria, the National Institute of Health in the USA recommended the two-step screening for GDM,
which has been adopted by the American College of Obstetrics and Gynecology (ACOG) [22,23].
In the two-step approach, women first undergo a 1-h 50-g glucose screen, and if it is abnormal, a 3-h GTT
with a 100-g glucose load is performed. If results are abnormal on the 3-h GTT, the patient is diagnosed
with GDM. Based on the one-step IADPSG screening criteria, 17.8% of pregnant patients in the USA
would test positive for GDM, which would nearly double the incidence of GDM in the USA [24].
The ACOG and other organizations in the USA have not adopted the one-step process due to a lack of
evidence of impact on the pregnancy outcomes. The two-step testing at 24–28 weeks’ gestation starts
with an initial screen in a non-fasting state, with an oral 50-g glucose load followed by a 1-h plasma
glucose level. The cutoff value for the 1-h glucose screen is 130 to 140 mg/dL. Screen-positive women
undergo the 3-h oral GTT. Following an overnight fast, a 100-g oral glucose load is administered.
Plasma glucose levels are checked in the fasting state and at 1 h, 2 h, and 3 h following the glucose
load [22]. Details of the different screening protocols are documented in Table 1.

Table 1. Protocol-based guidelines for diagnosis of gestational diabetes on oral glucose tolerance test.

Gestational
Glucose
Guidelines Age at FBS 1h 2h 3h
Load
Screening
IADPSG 2010 24–28 weeks 75 g <92 mg/dL <180 mg/dL <153 mg/dL -
Canada Diabetes <95 mg/dL <190 mg/dL <162 mg/dL
24–28 weeks 75 g -
Association 2018 <5.3 mmol/L <10.6 mmol/L <9.0 mmol/L
<101 mg/dL <140 mg/dL
NICE 2015 24–28 weeks 75 g -
<5.6 mmol/L <7.8 mmol/L
ACOG 2018 24–28 weeks 100 g <95 mg/dL <180 mg/dL <155 mg/dL <140 mg/dL

Early glucose screening is normally completed at the first prenatal visit in women with risk factors
that include obesity with a BMI of ≥30 Kg/m2 , history of gestational diabetes in a prior pregnancy,
known impaired glucose metabolism, hemoglobin A1C of ≥5.7%, first-degree relative with diabetes
mellitus, high-risk ethnicity, history of polycystic ovarian syndrome, pre-existing hypertension or
cardiovascular disease, or a prior large baby ≥4000 g [22]. The early screening helps detect patients
with pre-pregnancy type II diabetes mellitus. Women who have a normal glucose screen in early
pregnancy have the test repeated at 24–28 weeks’ gestation.
Plasma glucose levels drawn in a fasting state, followed by a glucose load. The normal levels
are as noted in the table. In the IADPSG, the Canada Diabetes Association, and the NICE guidelines,
GDM is diagnosed when one or more plasma glucose levels are elevated above the normal levels.
In the ACOG guidelines, patients with a positive 1-h glucose screen undergo the 3-h test and when
two or more levels are elevated above the normal levels, GDM is diagnosed.

5. Pathophysiology of Gestational Diabetes

Claes Hellerström has been credited for the early work starting in 1963 on pancreatic changes
during pregnancy and lactation in a mouse model (25,28). Insulin requirements physiologically increase
during pregnancy. The increase in insulin demand is due to increased maternal caloric intake, maternal
weight gain, presence of the placental hormones such as placental growth hormone, and placental
lactogen, as well as increased prolactin and growth hormone production. As the pregnancy advances,
the pancreatic β-cell mass increases to keep up with the demand for increased insulin. Failure of
the β-cell expansion with a relative inadequate rise in insulin secretion leads to GDM.
Maternal glucose is transported across the placenta to the fetus, and this delivery depends
on the concentration gradient between the fetus and the maternal glucose levels. In the later part
of pregnancy, the fetus diverts an increasing amount of maternal glucose towards itself, which leads to
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Int. J. Environ. Res. Public Health 2020, 17, 9573 4 of 12

across the placenta between the mother and the fetus, the maternal insulin resistance increases, as
well as the hepatic glucose production [25]. In turn, the β-cells increase insulin secretion to prevent
aexcessive
decrease delivery of glucose
in maternal glucose to the fetus.
levels. In order to maintain the concentration gradient of glucose across
the placenta between the mother and the fetus, the maternal insulin resistance increases, as well as
6. Management
the of production
hepatic glucose Gestational[25].
Diabetes
In turn, the β-cells increase insulin secretion to prevent excessive
delivery of glucose to the fetus.
The approach to optimal management of a patient diagnosed with GDM requires a
multidisciplinary approach. This includes teaching patient self-monitoring of blood glucose levels,
6. Management of Gestational Diabetes
dietary modifications and nutrition monitoring, lifestyle changes, and maternal weight gain
The approach
management. Up totooptimal
70–85%management of a patient with
of patients diagnosed diagnosed with GDM
gestational requires
diabetes canabe
multidisciplinary
managed with
approach.
adequate This includes
physical teaching
activity, andpatient self-monitoring
dietary and lifestyle of blood glucose[26].
modifications levels,
In dietary
15–30%modifications
of patients,
and nutritionwill
medications monitoring, lifestyle
be required. Thesechanges, and maternal
medications weightasgain
include insulin wellmanagement. Up to 70–85%
as oral hypoglycemic agents
of patients
(Figure 1). diagnosed with gestational diabetes can be managed with adequate physical activity, and
dietary and lifestyle modifications [26]. In 15–30% of patients, medications will be required. These
medications include insulin as well as oral hypoglycemic agents (Figure 1).

Lifestyle Changes
Diet, Physical Activity

Inadequate Adequate
Glucose Control Glucose Control
15–30% 70–85%

Continue Diet
Insulin Primary Secondary Modifications
Option Options and Physical
Activity
Rapid acting
Long acting Short/Intermediat Aspartate
e acting Metformin Glyburide
Glargine (Lantas) (Novolog) and
Detemir (Levemir) Regular and NPH Lispro
(Humolog)

Figure 1. Management of hyperglycemia in gestational diabetes.

7. Blood Glucose Monitoring

Figure 1. Management of hyperglycemia in gestational diabetes.

Most organizations recommend daily self-glucose monitoring at home. Currently, the recommendations
7. Blood Glucose Monitoring
include daily self-monitoring with fasting and postprandial blood glucose. The ADA recommends
Most organizations
the following target values: recommend
a fasting blooddaily
glucose of <95 mg/dL
self-glucose monitoring at home.
and a one-hour Currently,
postprandial the
blood
glucose of <140 mg/dL
recommendations include daily self-monitoring
or a two-hour postprandial with
bloodfasting of <120
glucoseand postprandial blood glucose.
mg/dL. Pre-prandial The
glucose
ADA recommends
monitoring the following
is primarily target
for those with values: a fasting
pre-existing blood
diabetes. glucose of
Monitoring <95hemoglobin
with mg/dL and A1C
a one-hour
levels
postprandial
is bloodfor
not as valuable glucose of <140
assessing mg/dL
glucose or a two-hour
control in GDMpostprandial
[27]. Studiesblood
haveglucose of <120
examined mg/dL.
alternative
Pre-prandial
testing glucose
approaches monitoring is primarily
to self-monitoring, such as for those with pre-existing
healthcare-based monitoring diabetes. Monitoring
and continuous with
glucose
hemoglobin A
monitoring. A1C levels is
Cochrane not asreported
review valuable forthere
that assessing glucose
were no controlinin
differences GDM [27]. Studies
self-monitoring have
compared
examined
with alternative testing
healthcare-based glucoseapproaches
monitoringtofor
self-monitoring,
both maternal such as healthcare-based
and neonatal monitoring
complications. and
There were
continuous
also glucosebetween
no differences monitoring. A Cochraneand
self-monitoring review reportedglucose
continuous that there were noin
monitoring differences in self-
cesarean section
monitoring
rates, large forcompared
gestationalwith
age,healthcare-based glucose monitoring
or neonatal hypoglycemia [28]. for both maternal and neonatal
complications. There were also no differences between self-monitoring and continuous glucose
8. Dietary Interventions
monitoring in cesarean section rates, large for gestational age, or neonatal hypoglycemia [28].
Nutritional therapy must be discussed with a patient and, ideally, a diabetes educator counsels
the patient Interventions
8. Dietary regarding dietary modifications. General guidance in pregnancy is for women to consume
three Nutritional
meals and therapy
two snacks
mustduring the day.
be discussed Meal
with plansand,
a patient can ideally,
be developed between
a diabetes thecounsels
educator patient
and the dietary educator to meet the appropriate daily requirements for pregnant diabetic
the patient regarding dietary modifications. General guidance in pregnancy is for women to consume patients,
while
three trying
meals to incorporate
and foods
two snacks that are
during the enjoyed by the
day. Meal patient
plans as developed
can be well feasiblebetween
for the patient to follow.
the patient and
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In conjunction with diet, women should be advised to write down their meals with their blood glucose
values to help them identify foods that may contribute to postprandial hyperglycemia.
There are a variety of dietary approaches that have been described in the literature,
including calorie-restricted diets, low-glycemic index diets, the DASH diet (dietary approaches
to stop hypertension), low-carbohydrate diets, and low-unsaturated fat diets, high-fiber diets,
and soy-based diets. Most of the dietary studies in pregnancy are reported to be of low-quality
evidence [29]. ACOG references a 1993 study suggesting that the daily calorie allotment for gestational
diabetics be distributed by percentages between the macronutrients with 40% from carbohydrates,
20% protein, and 40% fat [22]. However, the ADA’s 2017 review on diabetes care recommended similar
dietary guidance for gestational diabetics to women with pre-existing diabetes. Fat consumption
guidelines, cited from the Institute of Medicine, state that 20–35% of calories should be from fat.
Higher-quality complex carbohydrates with lower glycemic indexes are preferred since they may
help reduce the need for insulin as well as decrease postprandial hyperglycemia [30]. High-protein
diets have not been demonstrated to improve health or glycemic control, and some studies suggest
that excessive protein intake is associated with low fetal birthweight [30]. The ADA recommends
daily protein requirements of 1–1.5 g/kg or 15–20% of consumed calories. Based on the above
resources, dietary education should emphasize a balanced diet with portion control, healthy fats,
complex carbohydrates, and 20% protein.

9. Physical Activity
Exercise and physical activity are supported and encouraged during pregnancy, including in
women with GDM. Moderate exercise during pregnancy has many beneficial effects including lower
risk for development of GDM, lower likelihood of large for gestational age neonates, and being
associated with lower hypertensive disorders and preterm birth, without an increase in fetal growth
restriction [31,32]. Additionally, lifestyle changes during pregnancy have an influence on the postpartum
period by lowering the risk of postpartum depression [33]. Current recommendations are for 30 min of
moderate-intensity exercise, 5 days a week. When unable to perform moderate exercises, women may
consider light exercises such as post-meal walks for 10–15 min, which can have a beneficial impact on
blood sugar control. Pregnant women should avoid high-impact activities since they could result in
abdominal trauma.

10. Pharmacotherapy for Management of Gestational Diabetes

In up to 15–30% of patients with GDM, despite recommended diet and lifestyle modifications,
blood glucose control is inadequate, and pharmacotherapy is required [34]. There are no well-studied
protocols to determine the optimal time to initiate pharmacotherapy for glycemic control. Typically,
after a period of 10–14 days of dietary and lifestyle modifications, if hyperglycemia persists through
the day, pharmacotherapy should be considered. Based on a multicenter randomized trial by
the NICHD, if the majority of fasting or postprandial blood glucose measurements are elevated or if
there is suspicion of hyperglycemia with a random blood glucose level of ≥160 mg/dL or a fasting level
of ≥95 mg/dL, medications should be initiated [35].
Insulin as well as oral medications has been used for the management of hyperglycemia in
GDM patients. During pregnancy, insulin has the safest profile. The oral agents that have been
studied include sulfonylurea such as glyburide (also known as glibenclamide), as well as metformin.
In the USA, both the ADA and ACOG recommend insulin as the first line for control of hyperglycemia
in patients with GDM. Insulin is a large molecule and does not cross the placenta. Metformin and
glyburide have been shown to cross the placenta and into the fetus.

11. Insulin Regimens

In patients that require insulin, the dose and timing of administration depend on the patient’s
body weight, gestational age, and the time of day at which hyperglycemia is occurring. Once initiated,
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insulin doses are adjusted frequently throughout the pregnancy based on blood glucose results,
symptomatic hypoglycemia, physical activity, dietary consumption, infection, and compliance.
Insulin was discovered in 1922. In 1946, the intermediate-acting NPH insulin was introduced. For a
long period of time, NPH was being used. Since then, research in different types of available insulin has
evolved significantly. The insulin analogs that are currently available include rapidly acting analogs,
such as aspart (Novolog) and lispro (Humalog), short-acting regular insulin, intermediate-acting NPH
insulin, or longer-acting insulin analogs such as glargine (Lantus) and detemir (Levemir). In GDM,
short-acting insulin is reported to increase the possibility of hypoglycemia and may cause fluctuations
in glycemic control. Recent experience with aspart has been reassuring, while lispro has been associated
with higher birth weight and increased rates of large for gestational age neonates [36]. For intermediate-
and longer-acting insulin, randomized trials comparing detemir to NPH revealed no difference between
the two in regard to glucose control and perinatal outcomes. Detemir has been associated with a lower
incidence of hypoglycemia in the non-pregnant diabetic [37].
Two main approaches to prescribing insulin are based on the specific timing of recurrent
hyperglycemia. Insulin can be administered throughout the day in divided doses or be given as a single
daily dose depending on the timing of hyperglycemia. In women experiencing hyperglycemia only in
the morning fasting state, intermediate insulin, such as NPH, or detemir should be administered at
bedtime, as a single dose. In women experiencing postprandial hyperglycemia following specific meals
only, rapid-acting insulin should be considered prior to the meal. Women experiencing hyperglycemia
throughout the day should be managed with a combination of intermediate- or long-acting and
short-acting insulin, with the total daily dose of insulin of 0.7–1.0 unit/Kg divided into rapid-acting
insulin given before meals and intermediate- or long-acting insulin in the morning or at bedtime [22].
When prescribing insulin, close blood glucose monitoring is needed to try to avoid periods of
hypoglycemia or hyperglycemia. Patients are advised to bring their self-monitored blood glucose logs
to the office so the provider can determine if changes in the insulin regimen are needed.

12. Oral Hypoglycemic Agents

Oral medications have not been adequately studied for possible long-term effects on neonatal
outcomes, and therefore they are not recommended as the first choice in treatment for persistent
hyperglycemia in GDM patients. These are also reported to fail in controlling hyperglycemia in about
a quarter of women with GDM. In instances where patients are unable to get insulin, or refuse insulin,
oral medications may be prescribed. When comparing the two oral agents, metformin appears to
be safer than glyburide. Glyburide has been associated with neonatal hypoglycemia and higher
birth weight, which can increase the risk for shoulder dystocia and need for cesarean delivery [38,39].
Additionally, glyburide is demonstrated to be present in umbilical cord blood samples in concentrations
that are 50–70% those of maternal levels which can lead to neonatal hypoglycemia [38]. Even though
metformin is stated to have a lower risk of neonatal hypoglycemia, the umbilical cord blood levels of
metformin are reported to be similar to or higher than maternal levels [34].
Metformin dose starts at 500 mg orally each night or 500 mg twice daily based on glycemic control.
Maximum total daily dose is 2500–3000 mg during pregnancy, which is higher than in the non-pregnant
state. Glyburide is started at 2.5 mg daily or every 12 h and gradually increased to a maximum of 10 mg
twice daily, based on glycemic control [22]. In pregnancy, the serum concentration of glyburide rises
about 30–60 min after oral administration and peaks in 2–3 h, with the peak concentration coinciding
with the peak of blood glucose following a meal. Since glyburide peaks at 2–3 h after administration,
higher blood glucose values may be observed when checked 1 or 2 h following a meal, with a decrease
subsequent to that. This may lead to increasing the glyburide dose but with a negative subsequent
effect of hypoglycemia since the peak activity is 2–3 h following a meal [40]. When optimal glucose
control on oral agents cannot be achieved, the option of insulin should be re-addressed with the patient.
Int. J. Environ. Res. Public Health 2020, 17, 9573 7 of 12

13. Maternal and Fetal Complications

Gestational diabetes has a strong impact on maternal and fetal outcomes. Women with GDM
are at increased risk for development of pre-eclampsia and increased need for delivery by cesarean
section. Much of this risk is related to the degree of glycemic control during the pregnancy, with poor
glycemic control leading to higher risk for poor obstetrical outcomes [41]. These risks include
obstetrical and neonatal complications such as preterm delivery, polyhydramnios, macrosomia,
shoulder dystocia, admission to the neonatal intensive care unit, neonatal respiratory distress syndrome,
fetal hypoglycemia, and hyperbilirubinemia [42]. There is also an increase in the risk of stillbirth.
Aside from pregnancy-related risks, women diagnosed with gestational diabetes are at increased risk
of developing type 2 diabetes mellitus later in life.

14. Antepartum Surveillance

The need for fetal assessment is primarily based on maternal glycemic control. In women
with good glycemic control on diet alone, fetal testing prior to 40 weeks’ gestation is not indicated,
unless there are other indications [22]. If the patient is not delivered by the estimated due date,
fetal testing can be performed weekly or twice weekly beginning at 40 weeks’ gestation.
In women requiring pharmacotherapy, antepartum fetal testing should be initiated by
32 weeks’ gestation, consisting of a biophysical profile and non-stress test. These tests are performed
twice weekly, similar to women with pre-existing diabetes, and until delivery [43]. Presence of other
maternal co-morbidities or development of hypertensive disorders may impact the frequency and
timing of antepartum testing, with some patients requiring fetal monitoring earlier than 32 weeks [22].
There is no clear consensus on ultrasound examinations for fetal growth assessment, but it must be
performed at least once in the third trimester and closer to delivery to assess fetal growth. In summary,
antepartum fetal monitoring is based on glycemic control, the use of medical therapy, and the presence
of additional risk factors. Each institution should develop guidelines that are feasible based on
the resources and facilities at that institution.

15. Delivery Planning

ACOG published guidelines outlining the timing of delivery in women with gestational diabetes,
which is based on glycemic control. When GDM is well controlled with diet and exercise, delivery
should be considered starting at 39 weeks. Women requiring medications and with good glucose
control are delivered between 39 and 39-6/7 weeks’ gestation. There is less firm evidence on the timing
of delivery in women with poorly controlled GDM, which can be considered between 37 and
38-6/7 weeks’ gestation, taking into account the presence of other risk factors. In women with poor
glycemic control but reassuring fetal testing, delivery in the preterm period is not recommended.
The presence of hypertensive disorders, other co-morbidities, and non-reassuring fetal testing will
alter the delivery timing [22].
In women with GDM and an estimated fetal weight of ≥4500 g on an ultrasound exam,
the recommendation for cesarean is not well established [44]. In GDM cases with suspected
fetal macrosomia, along with being counseled regarding the risks of possible shoulder dystocia with
vaginal delivery, benefits and risks of cesarean delivery should also be discussed [22,45]. The timing
and anticipated route of delivery should be reviewed with a patient during the third trimester.

16. Intrapartum Glucose Management

During labor, women who have required insulin for GDM may have their blood glucose levels
checked every hour or less frequently, depending on the antepartum requirements. Women that
are diet-controlled can have less frequent blood glucose monitoring during labor, about every 4 h.
Based on the findings of a recent randomized controlled trial of GDM patients in labor, blood sugar
levels in the range of 60–120 mg/dL are acceptable. In the trial, tight intrapartum blood glucose
Int. J. Environ. Res. Public Health 2020, 17, 9573 8 of 12

control with a maternal blood glucose levels of 70–100 mg/dL was compared to more liberal control of
60–120 mg/dL. It was found that there was no difference in neonatal glucose concentrations between
the two groups [46]. Based on the results of the study, when the blood glucose levels during labor are
>120 mg/dL, intrapartum insulin must be considered.
The starting dose or rate of intrapartum insulin is generally based on the severity of the elevated
blood glucose value. If an insulin infusion is started, hourly blood glucose levels should be checked
with the insulin rate adjusted based on the hourly blood glucose level. Insulin is infused in a 5%
Dextrose solution or normal saline 0.9% (NS) at 125 mL/hour. The 5% glucose can be exchanged with
NS if the blood glucose level is persistently greater than 180 mg/dL. Insulin infusions can be used for
women undergoing both vaginal and cesarean delivery; however, in patients undergoing cesarean
section, a one-time subcutaneous insulin injection can be considered to achieve euglycemia at the time
of delivery. This management is one of many options to ensure euglycemia in the mother prior to
delivery. There are a variety of other protocols that have been described in the literature to optimize
intrapartum glucose control and the insulin protocol used may vary by institution.

17. Postpartum
Following delivery, insulin and oral agents should be discontinued. In the immediate postpartum
period, a fasting blood glucose level can be checked to determine if the patient has persistent
hyperglycemia. A fasting plasma glucose level of ≥126 mg/dL or postprandial level of ≥200 mg/dL
confirm persistent hyperglycemia. These patients are recommended to continue the diet modifications
and lifestyle changes and may need to be treated with pharmacological agents. Insulin or glyburide can
be prescribed in the postpartum period even in breast-feeding mothers, without concern for neonatal
side effects [47].
In women with GDM, the risk for subsequent development of type II diabetes mellitus is estimated
to be 10 times the control population, at 16.15% when followed up for 10 years. Some studies show
the risk to be as high as 60% [47,48]. Postpartum fasting blood glucose often fails to identify patients
with impaired glucose tolerance and those with type 2 diabetes mellitus. The Fifth International
Workshop on Gestational Diabetes recommends women complete a 75-g 2-h oral glucose tolerance test
at 6 to 12 weeks after delivery [44]. A fasting plasma glucose level of <100 mg/dL and a 2-h post-load
plasma glucose level of <140 mg/dL are considered normal. When the fasting plasma glucose level
is 100–125 mg/dL or the 2-h post-load glucose level is 140–199 mg/dL, the patient is considered to
have impaired glucose tolerance. When the fasting plasma glucose level is ≥126 mg/dL or the 2-h
post-load level is ≥200 mg/dL, the patient is diagnosed with diabetes mellitus. Recent data support
performing the 2-h glucose tolerance test in the immediate postpartum period while the patient is
still hospitalized [49]. This immediate postpartum glucose screening has not become standardized
yet and this approach should be individualized based on the patient population and resources in the
community. In conclusion, postpartum women need to be reminded of the importance of postpartum
follow-up for the development of type II diabetes mellitus.
There are limitations to this review. Due to the vast amount of literature published on the subject,
by various countries, it is possible that some important publications may have not been included in
this review. The review was limited to the management of gestational diabetes in the United States,
and this may differ in other countries where the incidence of obesity may be lower and resources
available to patients may be different.

18. Discussion
Based on the published literature, we have reviewed the history of GDM, screening options,
and management, with focus on the management options for persistent hyperglycemia. We report an
increasing incidence of diabetes and GDM in association with increasing incidence in maternal obesity.
Prevalence of GDM in the US has increased from <1% in 1961 to about 10%, using the two-step
GTT for screening. With the introduction of the one-step 2-h 75-g GTT recommended by the IADPSG,
Int. J. Environ. Res. Public Health 2020, 17, 9573 9 of 12

about 18% in the US would qualify as having GDM (13–15). Due to a lack of evidence of improvement in
pregnancy outcomes based on the one-step GTT, pregnant patients in the US continue to be screened at
24–28 weeks with the two-step GTT as recommended by the ACOG. Patients not previously diagnosed
with diabetes mellitus but with risk factors for developing GDM are recommended to be screened
earlier in gestation, and if negative, the screen is repeated at 24–28 weeks.
Patients with GDM are followed closely with self-monitoring of blood glucose levels, and lifestyle
changes which include modification in diet and exercise. In those with persistent hyperglycemia despite
lifestyle changes, treatment with medications must be considered. Due to potential maternal and
perinatal side effects of the oral hypoglycemic agents, insulin is the preferred treatment. Insulin regimens
consist of short-, intermediate-, and long-acting insulin. The type, dose, and timing of insulin are
determined by the timing and severity of hyperglycemia, and treatment is customized for each
patient. Patients are followed closely, and the dose of insulin is adjusted at regular intervals based on
the patient’s blood glucose levels.
In patients unable to take insulin, oral hypoglycemic agents can be considered. Metformin
is preferred over glyburide due to the risk of possible neonatal hypoglycemia associated with
maternal administration of glyburide. Typically, the dose of oral medications is once or twice a day,
with increments in doses based on the degree, timing, and persistence of hyperglycemia.
In patients requiring medications for persistent hyperglycemia, due to increased perinatal risks,
fetal wellbeing tests are initiated by 32 weeks’ gestation. In patients that are well-controlled GDM on
medications, delivery should be planned at 39 weeks and not earlier. However, in cases of maternal
complications, poorly controlled hyperglycemia, or non-assuring fetal testing, the delivery may be
considered earlier.
Due to the increased incidence of impaired glucose tolerance or type 2 diabetes mellitus in
patients with GDM, patient must be screened for diabetes in the postpartum period using the 2-h GTT.
Long-term risk for development of type 2 diabetes mellitus is high. For early diagnosis of type
2 DM and to prevent long-term effects of diabetes mellitus, regular follow-up exams and testing, at a
minimum of every 1–3 years, are recommended.
Among high-risk patients that test positive for GDM on early GTT, some may indeed have type
2 diabetes mellitus that was previously undiagnosed. The ideal screening test in this population
is not known as well as how early it should be administered. Patients diagnosed with GDM prior
to 20 weeks are frequently managed similar to those with type 2 diabetes mellitus, but data on
the pregnancy outcomes and perinatal outcomes in this group have not been well studied. Future
studies on pregnancy outcomes in this population will become increasingly important, as the maternal
obesity rates continue to rise. Whether obesity independently compounds the pregnancy risks in
patients diagnosed with early onset of hyperglycemia is also an area of research.

Author Contributions: Both authors contributed equally to the methodology, resources, data collection, writing,
review and editing. A.R. is the senior author. The literature review, resources, data curation, writing and editing,
and visualization were performed by authors A.R. and M.L. No methodology, software, validation, analysis,
investigation, and data curation. Supervision of the project was conducted by A.R. No funding acquisition was
conducted for this project. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Conflicts of Interest: The authors declare no conflict of interest.

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